Color-coded and sized loadable polymeric particles for therapeutic and/or diagnostic applications and methods of preparing and using the same

• US 9,107,850 B2
• Filed: 10/26/2007
• Issued: 08/18/2015
• Est. Priority Date: 10/25/2004
• Status: Active Grant

• Current Assignee: Varian Medical Systems Incorporated (Siemens AG)
• Original Assignee: Celonova Biosciences, Inc. (Boston Scientific Corporation)
• Inventors: Fritz, Ulf, Fritz, Olaf, Gordy, Thomas A., Wojcik, Ronald, Blmmel, Jacques, Kller, Alexander
• Primary Examiner(s): GULLEDGE, BRIAN M
• Application Number:
  US11/924,674
• Publication Number:
  US 20080113029A1
• Time in Patent Office: 2,853 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 9/5026 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: C08G 79/025 Polyphosphazenes
• CPC Class Codes: C08L 2666/02 Organic macromolecular compounds, natural resins, waxes or and bituminous materials
• CPC Class Codes: C08L 85/02 containing phosphorus

Abstract

Polymeric particles are provided for use in therapeutic and/or diagnostic procedures. The particles include poly[bis(trifluoroethoxy)phosphazene] and/or a derivatives thereof which may be present throughout the particles or within an outer coating of the particles. The particles may also include a core having a hydrogel formed from an acrylic-based polymer. Such particles may be provided to a user in specific selected sizes to allow for selective embolization of certain sized blood vessels or localized treatment with an active component agent in specific clinical uses. Particles of the present invention may further be provided as color-coded microspheres or nanospheres to allow ready identification of the sized particles in use. Such color-coded microspheres or nanospheres may further be provided in like color-coded delivery or containment devices to enhance user identification and provide visual confirmation of the use of a specifically desired size of microspheres or nanospheres.

Claims

1. Polymeric particles each comprising an acrylate polymer hydrogel core, a coating, and at least two water soluble organic dyes, wherein:

the coating comprises poly[bis(trifluoroethoxy)]phosphazene or a derivative thereof;

the polymeric particles are prepared to a known size; and

the at least two dyes impart a distinctive color to the polymeric particles based upon their known size;

wherein, based upon ionic interactions, one of the at least two water soluble dyes has an affinity for the core and another of the at least two water soluble dyes has an affinity for the coating.

2. The polymeric particles of claim 1, wherein the poly[bis(trifluoroethoxy)]phosphazene is poly[bis(2,2,2-trifluoroethoxy)]phosphazene or a derivative of poly[bis(2,2,2-trifluoroethoxy)]phosphazene.

3. The polymeric particles of claim 1, wherein the core contains one of the at least two dyes and/or the coating contains another of the at least two dyes.

4. The polymeric particles of claim 1, wherein the core comprises a polymer selected from poly(methacrylic acid), poly(methyl acrylate), poly(methyl methacrylate), poly(ethyl methacrylate), poly(hexamethyl methacrylate), poly(hydroxyethyl methacrylate), poly(acrylic acid), poly(butyl acrylate), poly(2-ethylhexyl acrylate), poly(ethyl acrylate), poly(acrylonitrile), poly(trimethylolpropane triacrylate), a copolymer thereof, or a combination thereof.

5. The polymeric particles of claim 1, wherein the known sizes are calibrated to a size ranging from about 1 to about 10,000 nanometers in diameter.

6. The polymeric particles of claim 1, wherein the known sizes are calibrated to a size ranging from about 40 to about 1,000 nanometers in diameter.

7. The polymeric particles of claim 1, wherein the polymeric particles are bioabsorbable or nonbioabsorbable.

8. The polymeric particles of claim 1, wherein the polymeric particles are provided as spheres or microspheres.

9. The polymeric particles of claim 1, wherein the core further comprises one or more active agent.

10. The polymeric particles of claim 9, wherein the active agent comprises a contrast agent, a steroid, hormone, nucleic acid, antibiotic, antiseptic, analgesic, anti-neoplastic, anesthetic, or biological agent to produce a desired effect in mammalian tissues into which the polymeric particles are placed.

11. Polymeric particles each comprising a core, a coating, and at least two water soluble organic dyes, wherein:

a. the coating comprises poly[bis(trifluoroethoxy)phosphazene] and/or a derivative thereof and substantially encloses the core;

b. the core comprises an acrylate polymer hydrogel; and

c. the polymeric particles are prepared to a known size;

wherein the at least two dyes impart a distinctive color to each polymeric particle according to its known size;

wherein, based upon ionic interactions, one of the at least two water soluble dyes has an affinity for the core and another of the at least two water soluble dyes has an affinity for the coating.